Sex- and region-dependent neuroinflammation in Alzheimer's disease

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-04-17 DOI:10.1002/alz.14603

Maricedes Acosta-Martínez, Vanessa Carter, Aviram Nessim, Radha Panchal, Dora John, Jasbeer Dhawan, Thomas G. Beach, Geidy E. Serrano, Erin E. Sundermann, Anat Biegon

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引用次数: 0

Abstract

INTRODUCTION

Despite known sex differences in immune function and Alzheimer's disease (AD), most studies of neuroinflammation in AD have not been analyzed by sex.

METHODS

We performed quantitative in vitro autoradiography of hippocampus, entorhinal cortex, and parietal cortex using [³H]-PK1195 and [¹⁸F]-T807. Proinflammatory microRNA (miRNA) expression in parietal cortex was measured by quantitative polymerase chain reaction (qPCR).

RESULTS

We found significant, region-dependent elevations of translocator protein (TSPO) density in AD relative to cognitively normal (CN) and mild cognitive impairment (MCI) in women but not men. Density of tau was increased in AD relative to CN and MCI in both sexes, but only women showed a significant positive correlation between tau and TSPO density. The expression of proinflammatory miRNAs was also significantly increased in AD versus CN or MCI women but not men.

DISCUSSION

Women are more susceptible than men to AD/tau-related neuroinflammation, supporting a sex-specific re-examination of the effects of neuroinflammation-targeting interventions in AD.

Highlights

We show that neuroinflammation in Alzheimer's disease (AD) is modulated by sex in a region-specific manner.
Neuroinflammation was highest in the subiculum and significant only in women.
Inflammatory microRNAs (miRNAs) increased in the parietal cortex of women, but not men, with AD.
Deposition of tau was highest in the entorhinal cortex and significant in both sexes.
Density of tau and TSPO was positively and significantly correlated only in AD women.

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.